Michael Kleerekoper, MD, MACE, has joined the faculty at the University of Toledo Medical School where he is Professor in the Department of Internal Medicine and section chief of the Endocrinology Division. The author of numerous journal studies, Dr. Kleerekoper serves on the editorial boards for Endocrine Today, Endocrine Practice, Journal of Clinical Densitometry, Journal of Women's Health, Osteoporosis International and Calcified Tissue International. Dr. Kleerekoper is also a founding board member of the newly formed Academy of Women’s Health.

Just hope the wires don’t get crossed

I was given a subscription to Wired magazine as a holiday gift and the first issue I received, December ’09, had a fascinating health care story to report. It details the work of Dr. David Eddy and his team who have developed a complex computer program to simulate controlled clinical trials. That phrase does not do justice to the program which is apparently, in the minds of some, nothing short of spectacular. There are of course many naysayers who are quoted but I don’t have enough knowledge about the issues raised to have an opinion either way.

What I do know, and what I want to reiterate from a previous blog, is that we must all be careful about accepting without question the results of randomized, double-blind, placebo-controlled clinical trials (RCTs). RCTs provide some of the best clinical and therapeutic data available but their cost and time constraints limit the extent to which the data can be directly applied to the patient in your office right now.

In order to obtain the most definitive data in the shortest possible time, patients enrolled in many RCTs, particularly those evaluating a potential new therapy, are carefully screened such that as many potentially confounding variables as possible are excluded from the study. This is a must for these RCTs, otherwise they would almost certainly require more patients studied over longer periods to have sufficient data to correctly document that the therapy does or does not work as anticipated from the many years of research that precedes these RCTs.

To remove the study population one step further away from the patient in front of you, an experienced team of clinical trial monitors and clinical trial nurses are on hand to ensure that compliance with the therapy in question is optimized, as is compliance with turning up for all serial lab studies. In the real world of health care, how many of us have the time or manpower to accomplish that!

Next is the issue with coexistent conditions, with most trials excluding potential study subjects in whom a coexisting condition may put them at increased risk of an adverse event no matter how effective the therapy being evaluated might be. A critical determinant in patient eligibility is the ongoing use of nonstudy medications that may or may not affect the outcome of the clinical trial.

In summary, the most efficient and cost-effective way to conduct an RCT is to have the study groups, both placebo and active drug, as free of potentially confounding issues as possible.

How often does that happen in day-to-day clinical practice? Not very in my experience, particularly with respect to poly-pharmacy. Yet we don’t have too many options! Patients with diabetes, for example, are very likely to have a requirement for therapies to control blood pressure and dyslipidemia, not to mention renal, vascular and neurologic complications and associated therapy. Add obesity and associated degenerative joint disease and poly-pharmacy is rampant. It is unclear what proportion of patients with osteoporosis has a secondary cause of bone loss with active treatment, but it is not a trivial number.

None of the above is new so where is this leading to?

There is appropriate increasing awareness of the need to practice preventive medicine but I am concerned about the potential long-term effects of prevention programs that rely on medication. In the field of endocrinology alone there is a trend to lower the threshold where pharmacologic intervention is recommended –hypothyroidism, pre-diabetes, lipids, blood pressure, and of course “osteopenia”.

I know my bias is showing but I want to plug FRAX- the new tool in the osteoporosis field - that provides a 10-year probability of fracture risk in an individual patient. Two women with the same spine and/or hip bone density are likely to have different fracture risks that are dependent on factors other than BMD. If we could provide similar numerical information regarding risk of heart attack, stroke, peripheral vascular disease, etc. perhaps, and only perhaps, we could be more circumspect about poly-pharmacy.

A woman whose father suffered a stroke at age 76 but whose mother died peacefully at age 93 without ever having had a fragility fracture is likely to be more concerned about her BP and lipid profile than her BMD no matter how low it may be. With tools like this available to us, we are likely to be more circumspect about poly-pharmacy. Just imagine what that might do to compliance with therapy!

I have enough trouble typing with two fingers at a time so I know better than to even think about looking further into Dr. Eddy’s “Archimedes” programs. Let’s hear from our more technological savvy colleagues.